This invention relates to a contact lens made of donor corneal tissue, to a method of preparing that lens, and to a technique of placing the lens on the eye. The lens is made of donor corneal tissue that is acellularized by removing native epithelium and keratocytes. These cells are replaced with human epithelium and keratocytes to form a lens that has a structural anatomy similar to human cornea. The ocular lens is used to correct conditions such as astigmatism, myopia, aphakia, and presbyopia.
|
85. A method for correcting the vision of a human eye having a cornea with an anterior surface, comprising the steps of:
a) preparing the anterior of the cornea; and b) introducing the ocular device of any one claims 1-10, 11-30, 31-37, and 38-84 upon said prepared anterior surface.
38. An ocular lens device for introduction into an eye comprising:
a lens core comprising donor corneal tissue having a generally convex anterior surface and a posterior surface, and having replaced keratocytes in said lens core or replaced epithelial cells covering at least a portion of said anterior surface prior to introduction into said eye.
1. An ocular lens device comprising:
a lens core comprising donor corneal tissue having a generally convex anterior surface and a posterior surface, the lens core not having been frozen, lyophilized, or chemically treated by a fixative, and having replaced keratocytes in said lens core or replaced epithelial cells covering at least a portion of said anterior surface.
76. An ocular lens device for correction of presbyopia comprising:
a lens core comprising donor corneal tissue having a generally convex anterior surface and a posterior surface, having replaced keratocytes in said lens core or replaced epithelial cells covering at least a portion of said anterior surface, having a size and configuration selected to be corrective for presbyopia, and a generally circular lens core central region without correction.
4. The ocular lens device of
6. The ocular lens device of
8. The ocular lens device of
9. The ocular lens device of
10. The ocular lens device of
14. The ocular lens device of
16. The ocular lens device of
17. The ocular lens device of
18. The ocular lens device of
19. The ocular lens device of
20. The ocular lens device of
21. The ocular lens device of
22. The ocular lens device of
23. The ocular lens device of
24. The ocular lens device of
25. The ocular lens device of
26. The ocular lens device of
27. The ocular lens device of
29. The ocular lens device of
30. The ocular lens device of
31. The ocular lens device of
32. The ocular lens device of
33. The ocular lens device of
34. The ocular lens device of
37. The ocular lens device of
41. The ocular lens device of
43. The ocular lens device of
44. The ocular lens device of
45. The ocular lens device of
46. The ocular lens device of
47. The ocular lens device of
51. The ocular lens device of
53. The ocular lens device of
54. The ocular lens device of
55. The ocular lens device of
56. The ocular lens device of
57. The ocular lens device of
58. The ocular lens device of
59. The ocular lens device of
60. The ocular lens device of
61. The ocular lens device of
62. The ocular lens device of
63. The ocular lens device of
64. The ocular lens device of
66. The ocular lens device of
67. The ocular lens device of
68. The ocular lens device of
69. The ocular lens device of
70. The ocular lens device of
71. The ocular lens device of
72. The ocular lens device of
75. The ocular lens device of
77. The ocular lens device of
78. The ocular lens device of
79. The ocular lens device of
80. The ocular lens device of
81. The ocular lens device of
82. The ocular lens device of
84. The ocular lens device of
86. The method of
|
|||||||||||||||||||||||||||
This invention is in the field of ophthalmology. More particularly, it relates to a living contact lens made of donor corneal tissue, to a method of preparing that lens, and to a technique of placing the lens on the eye.
The visual system allows the eye to focus light rays into meaningful images. The most common problem an ophthalmologist or optometrist will encounter is that of spherical ammetropia, or the formation of an image by the eye which is out of focus with accommodation due to an improperly shaped globe. The ophthalmologist or optometrist determines the refractive status of the eye and corrects the optical error with contact lenses or glasses.
Many procedures have been developed to correct spherical ammetropia by modifying the shape of the cornea. Light entering the eye is first focused by the cornea, which possesses approximately 75% of the eye's overall refractory power. The majority of refractive operations involve either decreasing or increasing the anterior curvature of the cornea.
The procedures in early corneal refractive surgery such as keratophakia and keratomileusis were originally developed to correct myopia and involved removing a corneal disc from the patient with a microkeratome. The removed corneal disc was then frozen prior to reshaping the posterior surface with a cryolathe. After thawing, the disc was returned to the eye and secured with sutures.
Epikeratophakia, as described in U.S. Pat. No 4,662,881, is a procedure that involves inserting a precut donor corneal tissue lens with bevelled edges into corresponding grooves in recipient cornea. The lens is then sutured to the corneal bed. The donor lens is lyophilized and requires rehydration before placement on recipient cornea.
These techniques and their variations were generally considered to be unsuccessful due to frequent complications involving irregular astigmatism, delayed surgical healing, corneal scarring, and instability of the refractive result. The problems were attributed to the technical complexity of the procedures as well as to the distortion in architecture of the corneal tissue secondary to lens manipulation. For example, in epikeratophakia, epithelial irregularity is induced by lyophilization of the donor lens. Freezing of the lenticule in keratophakia and keratomileusis also causes severe damage to epithelial and stromal cells and disrupts the lamellar architecture of the cornea.
The present invention is a pre-fabricated lens made of donor corneal tissue obtained from tissue sources such as human or animal cornea. The lens is a corneal disc that is preferably shaped on the posterior surface generally to conform in shape to the eye's anterior surface. The inventive lens may be shaped by an ablative laser, e.g., by an excimer laser or other suitable laser. The corneal lenticule is living tissue that has not been frozen, lyophilized, or chemically modified, e.g., fixed with glutaraldehyde to crosslink corneal tissue. Pre-existing keratocytes are removed and then replaced with human keratocytes to decrease antigenicity. After removal of epithelium in the central zone of the recipient's cornea, the lens is placed on this zone in the same manner that a contact lens is placed on the eye.
Ocular lenses found in the prior art do not use native cornea, but are formulated using soluble collagen such as collagen hydrogels, e.g., polyhydroxyethylmethacrylate, or other biocompatible materials. For example, in U.S. Pat. No. 5,213,720, to Civerchia, soluble collagen is gelled and crosslinked to produce an artificial lens. In addition to hydrogels, U.S. Pat. No. 4,715,858, to Lindstrom, discloses lenses made from various polymers, silicone, and cellulose acetate butyrate.
In the cases where ocular lenses use corneal tissue, the lenses are either corneal implants or require a separate agent to adhere the lens to the corneal bed. U.S. Pat. No. 5,171,318, to Gibson et al., and U.S. Pat. No. 5,919,185, to Peyman, relate to a disc of corneal tissue that is partially or entirely embedded in stroma. The ocular lens device disclosed in U.S. Pat. No. 4,646,720, to Peyman et al., and U.S. Pat. No. 5,192,316, to Ting, is attached to recipient cornea with sutures. The corneal inlay described in U.S. Pat. No. 4,676,790, to Kern, is bonded to recipient cornea using sutures, laser welding, or application of a liquid adhesive or crosslinking solution.
The ocular lens device of this invention does not alter the anatomical structure of corneal tissue. U.S. Pat. No. 4,346,482, to Tennant et al., discloses a "living contact lens" consisting of donor cornea that has been anteriorly curved for correction of vision. However, this lens is frozen prior to reshaping on a lathe which results in stromal keratocyte death. U.S. Pat. No. 4,793,344, to Cumming et al., also describes a donor corneal tissue lens that is modified by treatment with a gluteraldehyde fixative that preserves the tissue and prevents lens swelling. This treatment alters the basic structure of the corneal lenticule by crosslinking the tissue.
Furthermore, the cited documents do not show any methods of lens preparation that remove native corneal tissue cells and replace them with cells cultivated from human cornea. My inventive device is devitalized of native epithelium and keratocytes to create an acellular corneal tissue, and then revitalized with human epithelium and keratocytes. An attempt to construct a so-called "corneal tissue equivalent" was shown in U.S. Pat. No. 5,374,515, to Parenteau et al. However, the collagen used in that "equivalent" is obtained from bovine tendon instead of from cornea. The added keratocytes and epithelium are also not from human sources. The tissue using these cell culturing procedures is also quite fragile.
An excimer laser is used to reform a cornea via the "laser in situ keratomileusis" (LASIK) procedure. In this technique, an excimer laser is used to perform stromal photoablation of a corneal flap or in situ photoablation of the exposed stromal bed. Studies have shown that the inaccuracy of correction by this procedure may be as much as one diopter from the desired value. Lenses (contacts and spectacles), in contrast, are able to correct within 0.25 diopters of the desired value.
U.S. Pat. No. 6,036,683, to Jean et al., shows the use of a laser to reshape the cornea. However, the laser changes the native structure of the cornea by irreversibly coagulating collagen. Post-laser relaxation of collagen is not possible with this treatment.
This invention is a pre-fabricated donor contact lens that adheres to recipient cornea without sutures. The lens preserves the anatomy of normal corneal tissue. The donor lens can be obtained from human and animal sources, is devitalized of native keratocytes and epithelium to create an acellular tissue, and then revitalized with human keratocytes and epithelium to maintain lens viability and decrease antigenicity. The inventive corneal overlay technique may be completed under local anesthesia as well as general anesthesia, and the availability of a precut lens will greatly decrease procedure time, patient cost, and risk of operative complications. The duration of healing will also be reduced due to the implementation of a lens already repopulated with keratocytes.
This invention is a pre-fabricated ocular contact lens device having a lens core made of donor corneal tissue from tissue sources such as human or animal cornea. The device has a generally convex anterior surface and a concave posterior surface. The stroma portion of the lens core may be repopulated with replaced keratocytes and the anterior surface is preferably covered with a replaced epithelium. The lens core adheres to recipient cornea without sutures.
The lens core may be variously used to correct astigmatism, myopia, aphakia, and presbyopia. The lens core may be made of transgenic or xenogenic corneal tissue and have a clarity at least 85% of that of human corneal tissue of a corresponding thickness. The lens core is not frozen, lyophilized, or chemically treated with a fixative. However, variations of the device may contain therapeutic agents, growth factors, or immunosuppressive agents.
Another component of the invention is a method for preparing the lens device. After sharp dissection of a lenticule from donor corneal tissue, the posterior surface is shaped using an ablative laser, such as an excimer laser or other suitable shaping lasers. Native epithelium and keratocytes are removed and then replaced with human epithelium and keratocytes.
Another portion of the invention is a method of corneal overlay that involves de-epithelialization of a portion of the anterior surface of the recipient cornea and placement of the inventive ocular lens device upon that anterior surface.
The eye is designed to focus light onto specialized receptors in the retina that turn quanta of light energy into nerve action potentials. As shown in
The cornea (100) is the portion of the corneo-scleral layer enclosing the anterior one-sixth of the eye. The smooth curvature of the cornea is the major focusing power of images on the retina (104) and it provides much of the eye's 60 diopters of converging power. The cornea is an avascular structure and is sustained by diffusion of nutrients and oxygen from the aqueous humor (106). Some oxygen is also derived from the external environment. The avascular nature of the cornea decreases the immunogenicity of the tissue, increasing the success rate of corneal transplants.
The cornea consists of five layers. The outer surface is lined by stratified squamous epithelium which is about 5 cells thick. Failure of epithelialization results in necrosis of the stromal cap and potential scarring of recipient cornea. The epithelium is supported by a specialized basement membrane known as Bowman's membrane, which gives the cornea a smooth optical surface. The bulk of the cornea, the substantia propria (stroma), consists of a highly regular form of dense collagenous connective tissue forming thin lamellae. Between the lamellae are spindle-shaped keratocytes which can be stimulated to synthesize components of the connective tissue. The inner surface of the cornea is lined by a layer of flattened endothelial cells which are supported by Descemet's membrane, a very thick elastic basement membrane.
As previously mentioned, the focusing power of the cornea is primarily dependent on the radius of curvature of its external surface. In myopia, as seen in
Inventive Lens Structure
The inventive contact lens is of a size and configuration that upon installation on the cornea, supplements the curvature of the cornea to correct conditions such as astigmatism, myopia, hyperopia, presbyopia, and aphakia. The lens core may comprise or consist essentially of acellular donor corneal tissue which has been re-vitalized and then placed on a de-epithelialized host cornea; the lens core is formed to correct refraction. The donor lenticule or lens core may be obtained from other human (allogeneic) or foreign tissue (xenogenic) sources, such as from rabbit, bovine, porcine, or guinea pig corneal tissue. Ocular lenses may also come from transgenic corneal tissue or corneal tissue grown in vitro. In all instances, the architecture of the corneal layers, the normal corneal tissue matrix, e.g., the connective tissue or the stroma, is preserved. The "corneal tissue matrix" is made up of thin layers of collagen fibrils. By the term "donor corneal tissue", as used here, is meant donor or harvested corneas or corneal tissue containing the "corneal tissue matrix". Additionally, it is highly desirable to preserve the anterior surface of the donated corneal tissue as found beneath the native epithelium. The donor corneal tissue is not to undergo treatments such as lyophilization, freezing, or other chemical fixation.
The ocular lens device of this invention desirably includes Bowman's membrane, where the donor tissue includes it, to maintain the native structure of human epithelium. Again, it is highly desirable to harvest from donor sources in such a way that the native anterior surface below the epithelium is preserved. I have found that these native structures have a superior ability, after the revitalization steps discussed below, to support and maintain the replaced epithelium also discussed below. Clarity of the inventive tissue lens core will be at least 85%, preferably between 75%-100%, and most preferably at least 90% of that of human corneal tissue of corresponding thickness.
The overall diameter of the inventive lens is generally less than about 25 mm and more preferably in between 10 and 15 mm. The thickness of the resulting lens is generally less than 300 μm, more preferably between 5-100 μm.
As shown in
As shown in
The annular ring may be situated on the lens core either by placement of a suitable dye, i.e., by "tattooing", or by placement of an opaque biocompatible member of, e.g., Dacron mesh or the like, on the posterior surface to filter light rays.
Shaping Step
Returning to
Sterilization, Devitalization, and Revitalization Steps
Although the order of the process steps outlined below is typical, it should be understood that such steps may be varied as needed to produce the desired result.
Generally, the lens will first be shaped to an appropriate shape as discussed above. The lens core may then be subjected to processes of sterilization, devitalization, and revitalization. Removal of epithelium (de-epithelialization) and keratocytes (acellularization) from the donor lens will be referred to as "devitalization". The addition of human epithelium and keratocytes will be referred to as "revitalization". One desirable method for accomplishing those steps is found just below. Other methods are known.
Phosphate buffered saline (PBS) with antibiotics, epithelial cell media, and keratocyte media are solutions used during these processes. The "PBS with antibiotics" solution may contain:
PBS with antibiotics
1. Amphotericin B (ICN Biomedicals) 0.625 μg/ml
2. Penicillin (Gibco BRL) 100 IU/ml
3. Streptomycin (Gibco BRL) 100 μg/ml
4. Phosphate buffered saline (Gibco BRL)
The composition of the epithelial cell media may include:
Epithelial cell media
1. Dulbecco's Modified Eagle Media/Ham's F12 media (Gibco BRL) 3:1
2. 10% fetal calf serum (Gibco BRL)
3. Epidermal growth factor (ICN Biomedicals) 10 ng/ml
4. Hydrocortisone (Sigma-Aldrich) 0.4 μg/ml
5. Cholera toxin (ICN Biomedicals) 10-10 M
6. Adenine (Sigma-Aldrich) 1.8×10-4 M
7. Insulin (ICN Biomedicals) 5 μg/ml
8. Transferrin (ICN Biomedicals) 5 μg/ml
9. Glutamine (Sigma-Aldrich) 2×10-3 M
10. Triiodothyronine (ICN Biomedicals) 2×10-7 M
11. Amphotericin B (ICN Biomedicals) 0.625 μg/ml
12. Penicillin (Gibco BRL) 100 IU/ml
13. Streptomycin (Gibco BRL) 100 μg/ml
The composition of the keratocyte media may include:
Keratocyte media
1. DMEM
2. 10% neonatal calf serum (Gibco BRL)
3. Glutamine (Sigma-Aldrich) 2×10-3 M
4. Amphotericin B (ICN Biomedicals) 0.625 μg/ml
Sterilization Step
After harvesting the lens core from donor corneal tissue and following the shaping step, the lens may be sterilized by immersion into 98% glycerol at room temperature. Three weeks of glycerol treatment inactivates intracellular viruses and any bacteria or fungi. Ethylene oxide gas sterilization may also be used, but tends to induce variable damage to stromal tissue.
Devitalization Step
De-epithelialization
Following sterilization, I prefer to de-epithelialize the donor lens by placing it in sterile PBS with antibiotics for four hours and changing the solution many times. The lens core may then be kept submerged in the PBS solution at 37°C C. for one week to produce a split between the epithelium and the stroma. The epithelium may then be removed, e.g., by physically scraping or washing with a liquid stream. Small numbers of lenses may be stripped of epithelium by gentle scraping with forceps.
Acellularization
The de-epithelialized lens may then be immersed in sterile PBS with antibiotics for an appropriate period, e.g., several weeks, perhaps six weeks to remove native keratocytes. The solution may be changed twice weekly. In some instances, it may not be necessary to remove keratocytes from the donor lens, e.g., when the donor tissue is obtained from a transgenic source and has minimal antigenicity.
Revitalization Step
Preparation of cells
Human epithelial cells and keratocytes are used in the revitalization process. Epithelial cells may be obtained from a tissue bank, but are preferably obtained from fetal or neonatal tissue. Fetal cells are most preferable, since the properties of fetal tissue minimize scarring during the wound healing process.
In any event, freshly isolated epithelial cells, obtained by trypsinization of corneal tissue, may be seeded onto a precoated feeder layer of lethally irradiated 3T3 fibroblasts (i.3T3) in epithelial cell media. Cells are cultured and media changed every three days until the cells are 80% confluent, about 7-9 days. Residual i.3T3 are removed with 0.02% EDTA (Sigma-Aldrich) before the epithelial cells are detached using trypsin (ICN Biomedicals). Another method of regenerating epithelium involves culturing autologous epithelial cells on human amniotic membrane as described in Tsai et al. (2000). "Reconstruction of Damaged Corneas by Transplantation of Autologous Limbal Epithelial Cells," New England Journal of Medicine 343:86-93.
Keratocytes may be extracted from the remaining stromal tissue. The stroma is washed in PBS, finely minced, and placed in 0.5% collagenase A (ICN Biomedicals) at 37°C C. for 16 hours. Keratocytes obtained from this enzyme digest are then serially cultured in keratocyte media. The epithelial cells and keratocytes generated in the revitalization step will be referred to as "replaced" epithelium and keratocytes.
Production of the Donor Lens
The acellular donor lens core may then be placed on a hydophilic, polyelectrolyte gel for completion of the re-vitalization. The preferred polyelectrolytes are chondroitin sulfate, hyaluronic acid, and polyacrylamide. Most preferred is polyacrylic acid. The lens is immersed in keratocyte media and incubated with approximately 3×105 keratocytes for 48 hours at 37°C C. Approximately the same amount of epithelial cells are then added to the anterior stromal surface. Tissue culture incubation continues for another 48 hours. Keratocyte media is changed every two to three days. Once the epithelium is regenerated, the polyelectrolyte gel draws water out of the lens at a pressure of about 20-30 mm Hg until the original lens dimensions are obtained.
Replaced epithelium covers at least a portion of the anterior surface and replaced keratocytes repopulate the stroma of the lens core after revitalization. It may be beneficial in some instances to incorporate therapeutic agents, growth factors, or immunosuppressive agents into the lens core to further decrease the risk of rejection or remedy disease states.
Placement of the Lens on the Eye
During the procedure, the donor lens (300) is placed on a portion of recipient cornea that has been de-epithelialized (308). The result is the construct (312) shown in FIG. 4B. The lens' replaced epithelium and the host epithelium eventually grow to form a continuous, water-tight layer (310). I have found that the inventive lens bonds to recipient cornea without sutures or adhesives, but can also be removed without substantial difficulty.
I have described the structural and physiologic properties and benefits of this donor ocular lens. This manner of describing the invention should not, however, be taken as limiting the scope of the invention in any way.
| Patent | Priority | Assignee | Title |
| 10092393, | Mar 14 2013 | ALLOTEX, INC | Corneal implant systems and methods |
| 10092594, | Mar 29 2012 | CXL OPHTHALMICS, LLC | Compositions and methods for treating or preventing diseases associated with oxidative stress |
| 10285857, | Sep 30 2010 | CXL OPHTHALMICS, LLC | Ophthalmic treatment device, system, and method of use |
| 10449090, | Jul 31 2015 | ALLOTEX, INC | Corneal implant systems and methods |
| 10555804, | Apr 04 2008 | NEXIS VISION, INC ; NEXIS VISION LIQUIDATING TRUST; JOURNEY1, INC | Therapeutic device for pain management and vision |
| 10555805, | Feb 24 2006 | RVO 2 0, INC | Anterior corneal shapes and methods of providing the shapes |
| 10575986, | Mar 29 2012 | CXL OPHTHALMICS, LLC | Ophthalmic treatment solution delivery devices and delivery augmentation methods |
| 10583041, | Mar 12 2015 | RVO 2 0, INC | Methods of correcting vision |
| 10596038, | Oct 23 2009 | NEXIS VISION LIQUIDATING TRUST; JOURNEY1, INC | Corneal denervation for treatment of ocular pain |
| 10627649, | Oct 23 2009 | NEXIS VISION LIQUIDATING TRUST; JOURNEY1, INC | Conformable therapeutic shield for vision and pain |
| 10663761, | Oct 23 2009 | NEXIS VISION LIQUIDATING TRUST; JOURNEY1, INC | Conformable therapeutic shield for vision and pain |
| 10729716, | Mar 29 2012 | CXL OPHTHALMICS, LLC | Compositions and methods for treating or preventing diseases associated with oxidative stress |
| 10751166, | Sep 02 2015 | Method for performing ophthalmosurgical operations using an autograft | |
| 10835371, | Feb 24 2006 | RVO 2 0, INC, D B A OPTICS MEDICAL | Small diameter corneal inlay methods |
| 10952900, | Jul 31 2015 | Allotex, Inc. | Corneal implant systems and methods |
| 11033429, | Sep 30 2010 | CXL OPHTHALMICS, LLC | Ophthalmic treatment device, system, and method of use |
| 11126011, | Apr 28 2011 | NEXIS VISION LIQUIDATING TRUST; JOURNEY1, INC | Contact lenses for refractive correction |
| 11135090, | Sep 30 2010 | CXL OPHTHALMICS, LLC | Ophthalmic treatment device, system, and method of use |
| 11497766, | Mar 29 2012 | CXL OPHTHALMICS, LLC | Compositions and methods for treating or preventing diseases associated with oxidative stress |
| 11931291, | Mar 29 2012 | EPION THERAPEUTICS, INC | Ophthalmic treatment solution delivery devices and delivery augmentation methods |
| 12070422, | Jul 31 2015 | Allotex, Inc. | Corneal implant systems and methods |
| 12156834, | Sep 30 2010 | CXL OPHTHALMICS, LLC | Ophthalmic treatment device, system, and method of use |
| 7004953, | Jul 23 2001 | FOS HOLDING S A | Device for separating the epithelium layer from the surface of the cornea of an eye |
| 7025455, | Dec 19 2003 | J&J Vision Care, Inc. | Multifocal contact lenses having a pinhole |
| 7156859, | Jul 23 2001 | FOS Holding S.A. | Device for separating the epithelium layer from the surface of the cornea of an eye |
| 7585075, | May 20 2004 | ForSight Labs, LLC | Corneal onlays and wavefront aberration correction to enhance vision |
| 7708750, | Jul 23 2001 | FOS Holdings S.A. | Device for separating the epithelium layer from the surface of the cornea of an eye |
| 7776086, | Apr 30 2004 | REVISION OPTICS, INC | Aspherical corneal implant |
| 7828844, | Sep 13 2002 | ForSight Labs, LLC | Inserting lenses into corneal epithelial pockets to improve vision |
| 7883520, | Apr 10 2006 | ForSight Labs, LLC | Corneal epithelial pocket formation systems, components and methods |
| 8057541, | Feb 24 2006 | REVISION OPTICS, INC | Method of using small diameter intracorneal inlays to treat visual impairment |
| 8162953, | Mar 28 2007 | REVISION OPTICS, INC | Insertion system for corneal implants |
| 8469948, | Aug 23 2010 | REVISION OPTICS, INC | Methods and devices for forming corneal channels |
| 8540727, | Mar 28 2007 | ReVision Optics, Inc. | Insertion system for corneal implants |
| 8668735, | Sep 12 2000 | REVISION OPTICS, INC | Corneal implant storage and delivery devices |
| 8900296, | Apr 20 2007 | RVO 2 0, INC, D B A OPTICS MEDICAL | Corneal inlay design and methods of correcting vision |
| 9005280, | Sep 12 2000 | ReVision Optics, Inc. | System for packaging and handling an implant and method of use |
| 9271828, | Mar 28 2007 | REVISION OPTICS, INC | Corneal implant retaining devices and methods of use |
| 9345569, | Oct 21 2011 | REVISION OPTICS, INC | Corneal implant storage and delivery devices |
| 9539143, | Mar 12 2015 | REVISION OPTICS, INC | Methods of correcting vision |
| 9549848, | Mar 28 2007 | REVISION OPTICS, INC | Corneal implant inserters and methods of use |
| 9555111, | Mar 29 2012 | CXL OPHTHALMICS, LLC | Ocular cross-linking system and method for sealing corneal wounds |
| 9566301, | Mar 29 2012 | CXL OPHTHALMICS, LLC | Compositions and methods for treating or preventing diseases associated with oxidative stress |
| 9622911, | Sep 30 2010 | CXL OPHTHALMICS, LLC | Ophthalmic treatment device, system, and method of use |
| 9877823, | Sep 16 2011 | ReVision Optics, Inc. | Corneal implant retaining devices and methods of use |
| 9889000, | Sep 12 2000 | ReVision Optics, Inc. | Corneal implant applicators |
| 9974646, | Sep 05 2012 | University of Miami | Keratoprosthesis, and system and method of corneal repair using same |
| 9987124, | Oct 21 2011 | ReVision Optics, Inc. | Corneal implant storage and delivery devices |
| ER6138, |
| Patent | Priority | Assignee | Title |
| 4346482, | Jan 22 1981 | Living contact lens | |
| 4646720, | Mar 12 1985 | Optical assembly permanently attached to the cornea | |
| 4662881, | Jan 21 1986 | Epikeratophakia process | |
| 4676790, | Sep 25 1985 | Method of manufacture and implantation of corneal inlays | |
| 4715858, | Jul 25 1986 | Epicorneal lens | |
| 4793344, | Nov 02 1987 | Recore, Inc. | Method for preparing corneal donor tissue for refractive eye surgery |
| 5171318, | Nov 09 1987 | Chiron Ophthalmics, Inc. | Treated corneal prosthetic device |
| 5192316, | Feb 16 1988 | Advanced Medical Optics, INC | Ocular device |
| 5213720, | Oct 16 1986 | CBS Lens, a California general partnership | Method of fabricating a collagen-hydrogel |
| 5374515, | Nov 13 1992 | PRESDENT AND FELLOWS OF HARVRD COLLEGE, THE | In vitro cornea equivalent model |
| 5522888, | Oct 06 1986 | CBS Lens, a California general partnership | Collagen-hydrogel for promoting epithelial cell growth and regeneration of the stroma |
| 5716633, | Oct 16 1986 | CBS Lens, a California general partnership | Collagen-hydrogel for promoting epithelial cell growth and regeneration of the stroma and artificial lens using the same |
| 5827641, | Nov 13 1992 | Organogenesis, Inc | In vitro cornea equivalent model |
| 5919185, | Apr 25 1997 | HEALTHCARE ROYALTY PARTNERS II, L P | Universal implant blank for modifying corneal curvature and methods of modifying corneal curvature therewith |
| 6036683, | Jan 02 1997 | G RODENSTOCK INSTRUMENTS GMBH | Process and apparatus for changing the curvature of the cornea |
| 6187053, | Nov 16 1996 | Process for producing a natural implant | |
| 6280435, | Mar 04 1998 | AMO Manufacturing USA, LLC | Method and systems for laser treatment of presbyopia using offset imaging |
| 6280469, | May 11 1999 | OREGON LIONS SIGHT & HEARING FOUNDATION, INC | Implantable iris device for the eye, and method of installing same |
| Executed on | Assignor | Assignee | Conveyance | Frame | Reel | Doc |
| Jul 18 2000 | Tissue Engineering Refraction, Inc. | (assignment on the face of the patent) | / | |||
| Mar 02 2006 | PEREZ, EDWARD | TISSUE ENGINEERING REFRACTION, INC | ASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS | 017275 | /0662 |
| Date | Maintenance Fee Events |
| Oct 06 2006 | M2551: Payment of Maintenance Fee, 4th Yr, Small Entity. |
| Nov 15 2010 | REM: Maintenance Fee Reminder Mailed. |
| Apr 08 2011 | EXP: Patent Expired for Failure to Pay Maintenance Fees. |
| Date | Maintenance Schedule |
| Apr 08 2006 | 4 years fee payment window open |
| Oct 08 2006 | 6 months grace period start (w surcharge) |
| Apr 08 2007 | patent expiry (for year 4) |
| Apr 08 2009 | 2 years to revive unintentionally abandoned end. (for year 4) |
| Apr 08 2010 | 8 years fee payment window open |
| Oct 08 2010 | 6 months grace period start (w surcharge) |
| Apr 08 2011 | patent expiry (for year 8) |
| Apr 08 2013 | 2 years to revive unintentionally abandoned end. (for year 8) |
| Apr 08 2014 | 12 years fee payment window open |
| Oct 08 2014 | 6 months grace period start (w surcharge) |
| Apr 08 2015 | patent expiry (for year 12) |
| Apr 08 2017 | 2 years to revive unintentionally abandoned end. (for year 12) |